title: Intracerebroventricularly applied peptidase inhibitors increase endogenous angiotensin levels.
abstract: Rats received the aminopeptidase inhibitors amastatin (AM) and bestatin (BE), and carboxypeptidase inhibitor Plummer's (PL) via intracerebroventricular infusion in various combinations, i.e. PL alone, AM + BE, and a cocktail consisting of AM + BE + PL. Blood pressure responses were recorded and a postinfusion sample of cerebrospinal fluid (CSF) was radioimmunoassayed for endogenous angiotensin levels. Results indicate that CSF angiotensin was increased approximately 1.5x over control levels when PL was infused; a 2.5x increase accompanied AM + BE administration; and a 10.3x elevation was measured when all 3 inhibitors were infused as a cocktail. Concomitant elevations in blood pressure accompanied increased concentrations of angiotensin. We conclude that endogenous levels of angiotensin can be significantly increased in the ventricular space when a combination of these inhibitors is utilized to protect both the amino and carboxyl terminals of the angiotensin molecule from enzymatic degradation.
authors.affiliation: Department of Psychology, Washington State University, Pullman 99164-6520.
authors.forename: C M
authors.initials: CM
authors.lastname: Batt
authors.forename: L L
authors.initials: LL
authors.lastname: Jensen
authors.forename: J M
authors.initials: JM
authors.lastname: Hanesworth
authors.forename: J W
authors.initials: JW
authors.lastname: Harding
authors.forename: J W
authors.initials: JW
authors.lastname: Wright
mesh_terms: D015097:3-Mercaptopropionic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000804:Angiotensin II / Q000134:cerebrospinal fluid*; D000805:Angiotensin III / Q000134:cerebrospinal fluid*; D000818:Animals; D000900:Anti-Bacterial Agents; D001794:Blood Pressure / Q000187:drug effects; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D007930:Leucine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology; D010455:Peptides; D011480:Protease Inhibitors / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000900:Anti-Bacterial Agents; D009842:Oligopeptides; D010455:Peptides; D011480:Protease Inhibitors; D000804:Angiotensin II; D000805:Angiotensin III; C016977:amastatin; C029729:2-mercaptomethyl-3-guanidinoethylthiopropionic acid; D015097:3-Mercaptopropionic Acid; D002268:Carboxypeptidases; D007930:Leucine; C012211:ubenimex